The presence of radioresistant hypoxic cells within human solid tumors is believed to be an important cause of local failure in radiotherapy. Many studies in experimetal animals have shown an enhancement of tumor radiation response and an increased probability of cure when irradiation occurred in the presence of hypoxic cell sensitizers such as misonidazole (Ro-07-0582). However several studies have indicated that the effective use of hypoxic cell sensitizers may be limited in the clinic by neurotoxic side effects such as peripheral neuropathy. Such side effects may limit the potential therapeutic gain and limit their use in the clinic. The goal of the research is to evaluate several nitroimidazole sensitizers which are either in current clinical use or which are potential candidates for this purpose in an effort to select the least neurotoxic agent and thereby improve the potential therapeutic ratio. One of the specific aims of the research is to establish a dose-response curve using quantitative functional tests in the mouse rich correlate to histological changes for the chronic administration of misonidazole and to repeat the process for other nitroimidazole sensitizers to determine if the dose response curves with single drugs can be discriminated from each other and to obtain a measure of their relative neurotoxicites. A secondary goal is concerned with biochemical studies which are directed towards obtaining information related to the mechanism of the neurotoxicity and which may provide data useful in the development of more sensitive and rapid assays for neurotoxicity in humans.